Nitric Oxide Shows Positive Signs in Clearing Hard-to-treat Mycobacterium Lung Infections in CF

Inhalation of nitric oxide as an add-on therapy may help reduce the burden of serious bacterial lung infections, namely the hard-to-treat Mycobacterium abscessus, in cystic fibrosis (CF) patients, AIT Therapeutics announced.

The study with that finding, “Pilot study to test inhaled nitric oxide in cystic fibrosis patients with refractory Mycobacterium abscessus lung infection,” was published in the Journal of Cystic Fibrosis.

Nitric oxide (NO) is a naturally occurring gas that has been shown to help the lungs resist pathogens by triggering the immune system. In fact, when applied directly to the airways, it can attract immune cells and has the potential to clear bacterial, fungal, and viral infections.

Infections by Mycobacterium abscessus, a multi-drug resistant nontuberculous mycobacteria that causes very aggressive and hard-to-treat lung infections, are common among patients with underlying lung conditions, including CF.

In a previous study, researchers showed that inhaled NO at 160 parts per million (ppm) for 30 min, five times a day for up to 26 days, reduced the Mycobacterium abscessus bacterial load and improved lung function in two CF patients.

Now, researchers evaluated the safety and effectiveness of inhaled NO in nine CF patients with hard-to-treat M. abscessus lung infection. Patients were given intermittent inhalations — 30 minutes each every four hours — of NO at 160 ppm as an add-on therapy to standard treatment (including antibiotics).

In total, patients received inhaled NO for 21 days, administered five times per day during hospitalization (14 days), and three times per day during ambulatory treatment (seven days).

The study’s main goal was to assess safety. Additional outcomes evaluated lung function and exercise tolerance, using the forced expiratory volume in one second (FEV1, a measure of how much air can be exhaled in one second after a deep inhaled breath) and 6-minute walk test (6MWT), respectively. Additionally, researchers evaluated the load of M. abscessus in the lung.

Results showed that at the end of the treatment, patients’ lung function and exercise capacity had increased compared to the start of the trial. This was observed in five and six patients out of nine, respectively.

The inhaled NO also reduced the bacterial load of M. abscessus infection, as shown by tests in the lab. One patient remained negative for the bacteria after up to 11 weeks after treatment. Moreover, inhalation of NO also cleared infection with the multi-drug resistant bacteria Pseudomonas aeruginosa in two out of five patients infected with both bacteria.

“We achieved our goal of demonstrating the safety and tolerability of inhaled nitric oxide in cystic fibrosis patients with Mycobacterium abscessus lung infection, and determined that further evaluation is warranted given the improvement shown in mean lung function, quality of life, physical function and M. abscessus load as shown by a downward trend in the sputum M. abscessus load measured during the study,” Lea Bentur said in a press release. Bentur is director of the pediatric pulmonary institute at Rambam Medical Center, Israel, and the study’s first author.

However, while “the study was not powered to demonstrate statistical significance,” Bentur added, “we believe intermittent NO at 160 ppm has the potential to demonstrate meaningful benefits to patients with cystic fibrosis where currently M. abscessus is an incurable chronic infection in most CF patients.”

Steven Lisi, chairman and CEO of AIT, added: “We are encouraged by the findings of this study and pleased to see the meaningful improvements in these patients. We believe our Nitric Oxide Generator and Delivery system could become an important treatment option for these patients as it may allow for a longer duration of treatment with patients self-administering at home.”

Of note, AIT Therapeutics developed a nitric oxide generator and delivery system, a patented drug-device combination that generates nitric oxide from normal air.